As a heterocyclic compound, the following compounds are known.    (1) As a PPAR ligand-receptor binder, a compound represented by the formula:
are each independently an aryl and the like; A is —O— and the like; B is —O— and the like; D is —O— and the like; E is a bond or an ethylene group; a, b, c and e are each 0-4; d is 0-5; f is 0-6; R1, R3, R5, R7, R9 and R11 are each independently a hydrogen and the like; R2, R4, R6, R8, R10 and R12 are each independently —(CH)q—X; q is 0-3; X is hydrogen and the like; Z is R21O2C— and the like; R21 is hydrogen and the like has been reported (WO 00/64876).    (2) As a compound that acts by binding to PPAR-α, PPAR-γ and PPAR-δ, a compound represented by the formula
wherein X is O, S or NH and R is methyl, ethyl, n-propyl, i-propyl, cyclopropyl, n-butyl, phenyl or —CH2OCH3, and a compound represented by the formula
wherein X is C or N and R is methyl, ethyl, n-propyl, i-propyl, —CH2OCH3 or —CO2CH3 have been reported (WO01/17994).    (3) As a retinoid related receptor function regulator, a compound represented by the formula
wherein R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a bond, O, S, —CO—, —CS—, —CR4(OR5)— or —NR6— (R4 and R6 are each a hydrogen atom or an optionally substituted hydrocarbon group and R5 is a hydrogen atom or a hydroxyl-protecting group); m is 0-3; Y is O, S, —SO—, —SO2—, —NR7—, —CONR7— or —NR7CO— (R7 is a hydrogen atom or an optionally substituted hydrocarbon group); ring A is an aromatic ring optionally further have 1 to 3 substituents; n is 1-8; ring B is a nitrogen-containing 5-membered heterocycle optionally further substituted by an alkyl group; X1 is a bond, O, S, —SO—, —SO2—, —O—SO2— or —NR16— (R16 is a hydrogen atom or an optionally substituted hydrocarbon group); R2 is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; W is a bond or a C1-20 divalent hydrocarbon residue; and R3 is —OR8 (R8 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR9R10 (R9 and R10 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted acyl group, or R9 and R10 are bonded to each other to form a ring) has been reported (WO01/38325).    (4) As a retinoid related receptor function regulator, a compound represented by the formula
wherein R1 is an optionally substituted 5-membered aromatic heterocyclic group;
X is a bond, an oxygen atom, a sulfur atom, —CO—, —CS—, —CR4(OR5)— or —NR6— (R4 is a hydrogen atom or an optionally substituted hydrocarbon group, R5 is a hydrogen atom or a hydroxyl-protecting group, R6 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
Q is a divalent hydrocarbon group having 1 to 20 carbon atoms;
Y is a bond, an oxygen atom, a sulfur atom, —SO—, —SO2—, —NR7—, —CONR7— or —NR7CO— (R7 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
ring A is an aromatic ring optionally further having 1 to 3 substituents;
Z is —(CH2)n-Z1- or -Z1-(CH2)— (n is an integer of 1 to 8, Z1 is an oxygen atom, a sulfur atom, —SO—, —SO2— or —NR16— (R16 is a hydrogen atom or an optionally substituted hydrocarbon group));
ring B is a pyridine ring, benzene ring or naphthalene ring, each optionally further having 1 to 3 substituents;
U is a bond, an oxygen atom, a sulfur atom, —SO— or —SO2—;
W is a divalent hydrocarbon group having 1 to 20 carbon atoms; and
R3 is —OR8 (R8 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR9R10 (R9 and R10 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted acyl group, or R9 and R10 are optionally bonded to form an optionally substituted ring):
provided that, when ring B is a benzene ring optionally further having 1 to 3 substituents, U is a bond has been reported (WO02/53547).
Peroxisome proliferator-activated receptor gamma (PPARγ), a member of the intranuclear hormone receptor superfamily, which is typically exemplified by steroid hormone receptors and thyroid hormone receptors, plays an important role as a master regulator in the differentiation of adipocytes with its expression induced in the very early stage of adipocyte differentiation. PPARγ forms a dimer with the retinoid X receptor (RXR) by binding to a ligand, and binds to a responsive site of the target gene in the nucleus to directly control (activate) transcription efficiency. In recent years, the possibility that 15-deoxy-Δ12.14 prostaglandin J2, which is a metabolite of prostaglandin D2, serves as an endogenous ligand for PPARγ, has been suggested, and it has been shown that a class of insulin resistance enhancers, typically exemplified by thiazolidinedione derivatives, possess ligand activity for PPARγ, and that its potency is proportional to its hypoglycemic action or adipocyte differentiation-promoting action (e.g., Cell, vol. 83, p. 803 (1995): The Journal of Biological Chemistry, vol. 270, p. 12953 (1995); Journal of Medicinal Chemistry, vol. 39, p. 655 (1996)).
In recent years, furthermore, it has been shown that 1) PPARγ is expressed in cultured cells of human liposarcoma origin, whose proliferation is ceased by the addition of a PPARγ ligand (Proceedings of the National Academy of Sciences of The United States of America, vol. 94, p. 237 (1997)), 2) nonsteroidal anti-inflammatory drugs, typically exemplified by indomethacin and fenoprofen, have PPARγ ligand activity (e.g., The Journal of Biological Chemistry, vol. 272, p. 3406 (1997)), 3) PPARγ is expressed at high levels in activated macrophages, with the transcription of a gene involved in inflammation inhibited by the addition of a ligand therefor (e.g., Nature, vol. 391, p. 79 (1998)), 4) PPARγ ligands suppress the production of inflammatory cytokines (TNFα, IL-1β, IL-6) by monocytes (e.g., Nature, vol. 391, p. 82 (1998)), 5) adipocyte hypertrophy, fat accumulation and expression of insulin resistance are suppressed in PPARγ hetero deficient mouse (e.g., Molecular Cell (1999), vol. 4, p. 597), 6) PPARγ ligand inhibits differentiation of 10T1/2 cell into adipocyte by PPARγ agonist (e.g., Proceedings of The National Academy of Sciences of The United States of America (1999), vol. 96, p. 6102), 7) PPARγ ligand suppresses differentiation of 3T3-L1 cell into adipocyte by PPARγ agonist (e.g., Molecular Endocrinology (2000), vol. 14, p. 1425) and the like.